Induction of the intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFR alpha) gene by the TR4 orphan receptor - A member of steroid receptor superfamily

A conserved hormone response element, CNTFR-DR1 (5'-AGGTCAGAGGTCAGG-3'), has been identified in the 5th intron of the alpha component of the ciliary neurotrophic factor receptor (CNTFR alpha) gene for the human TR4 orphan receptor (TR4). Electrophoretic mobility shift assay showed a specific binding with high affinity (K-d = 0.066 nM) between TR4 and the CNTFR-DR1. A reporter gene assay using chloramphenicol acetyltransferase demonstrated that the 5th intron of CNTFR alpha has an enhancer activity which could be induced by TR4 in a dose-dependent manner. Furthermore, our in situ hybridization data showed that abundant TR4 transcripts were detected in adult brain, in regions of cortical and hippocampal neurons, as well as in many developing neural structures, including brain, spinal cord, ganglia (sympathetic and sensory), and neuronal epithelia (retinal, otic, olfactory, and gustatory). The striking similarities in the expression patterns of TR4 and CNTFR alpha in the developing and postnatal nervous systems further support the potential role of TRA in neurogenesis. Collectively, these data suggest that the human CNTFR alpha gene could represent the first identified neural-specific gene induced by TR4.